PROJECT SUMMARY/ABSTRACT ? Applied Research Project The overall goal of the SMSR is to provide the tools and resources for complex trait analysis in mice. The ultimate goal of complex trait analysis is the identification of specific genes and pathways, which requires proof of causation. Causation is best demonstrated through replacement of specific allelic variants in their original context, recapitulation of allelic variants on an inbred strain background, and/or biochemical assays in engineered cell lines or stem cells. To advance the study of complex traits novel mouse populations, like the Diversity Outcross (DO), have been developed to allow for ultra high-resolution mapping. The small QTL that can be obtained through application of the DO population comes at an expense because individual DO genomes cannot be reproduced through standard husbandry or assisted reproductive technologies, and therefore individual DO genomes cannot be genetically engineered. The overall goal of the proposed applied research project is to explore methods for stabilization of extreme DO genomes through cloning. These methods include the derivation of iPS cells from adult fibroblasts and the production of 100% iPS cell derived chimeras. The establishment of these protocols within the SMSR will provide the foundation for a new service whereby the reagents for DO genome stabilization, candidate gene testing and proof of causation can be available through the resource.